17(20)-oxido-3,11alpha, 20-triacyloxypregnanes



Patented Mar. 2, 1954 UNITED STATES PATENT OFFICE 17 (20)-OPHDO-3,11a,20-TRIACYLOXY- PREGNANES Frank H. Lincoln, Jr., and GeorgeB. Spero, Kalamacoo, Mich., assignors to The Upjohn Company, Kalamazoo,Mich., a corporation of Michigan No Drawing. Application Serial No.

of the present invention the formula:

([3113 C- Ac AcO- CH3 I ration at the three-carbon atom includes bothalpha and beta forms.

It is an object of the present invention to provide a group of novelcompounds, the 17(29)- oxido-3,11a,20-triacyloxypregnanes, which haveutility in the preparation of biologically active compounds, such ascortisone and its derivatives, and which are also physiologically activeper se. A further object of the invention is the provision of a processfor the production of the 17(20)- oxido-3,lla,20-triacyloxypregnanesOther objects of the present invention will be apparent to those skilledin the art towhich this invention pertains. I The 17 (20) -'oxido-3,11a,20-triacyloxypregnanes are useful in the preparation of othersteroid compounds having an oxygen atom at carbon atom eleven, such ascortisone acetate, which may be obtained from the 17(20)-oxido-3,l1v.,20- triacyloxypregnanes by known methods, for example byhydrolysis of the groups at the three, eleven, seventeen, and twentypositions to obtain three, eleven, and seventeen-hydroxyl groups and atwenty-ketone group, oxidation of the three and eleven-hydroxyl groupsto ketone groups, introduction tion of a double bond at the fourposition. Such compounds-are of particular interest in the field ofsteroid research due to the biological activity of the cortical hormonesand certain known derivatives thereof. The importance of suchinof a21-acetoxy group, and introducn January 18, 1952,

267,198 Claims. (01. 260-239.55)

vestigation is moreover emphasized by the shortage ofadrenal corticalhormones, and the absence of any present suggestion for the alleviationof said shortage except through organic synthesis.

The 17(20) -oxido-3,l1a,20-triacyloxypregnanes which are of particularinterest are those compounds of the above generic formula wherein AcOrepresents an ester of the three, eleven, and

twenty-hydroxyl groups with an organic carboxylic acid containing up toand including eight carbon atoms. Among such acids are formic, acetic,propionic, butyric, valeric, hexanoic, heptanoic, octanoic,cyclopentanoic, cyclopentylpropionic, benzoic, toluic, and the like.Preferred are those ester groups derived from the loweraliphatic acids,especially those containing from one to eight carbon atoms, inclusive.The acids may also contain substituents, such as halo, alkyl, andmethoxy, which are non-reactive under the reaction conditions employed.The three, eleven, and twenty-ester groups may be the same, or two estergroups may be the same and one different, or all three ester groups maybe different, depending on the starting materials, since the estergroups of the 17(2U)-OXidO-3,11a,20 triacyloxypregnanes are unchangedfrom those in the starting materials.

According to the novel process of the present invention, the17(20)-oxido-3,1la,20-triacyloxypregnanes are prepared by an oxidationreaction in which an atom of oxygen is added to the 1.7(20) -ethyleniclinkage in a starting 3,1la,20 triacyloxy-l7(20)-pregnene. Any oxidantor epoxidizing agent capable of furnishing the necessary oxygen may beemployed. The agents most commonly used are the organic peracids orhydrogen peroxide. Organic peraoids such as perac etic, perpropionic,perbutyric, perbenzoic, chloroperacetic, and others may be advanta-"geously employed; Concentrated hydrogen peroxide (H202) may likewise beutilized in the form bf a twenty to ninety per cent by weight aqueoussolution, a thirty per cent solution being preferred. The ratio ofoxygen-furnishing agent to starting steroid can be varied considerablywithin broad ranges. Ratios of up to ten moles or more of the peracid orconcentrated hydrogen peroxide to one moleof the starting enol ester areoperative, with ratios of from two to about six moles being preferredfor attainment of optimum results, the precise ratio being preferablyvaried inversely with the reaction time employed. The reaction iscarried'out by mixing together the starting 3,1la,20-triacyloxy-17(20)pregnene and the peracid of choice, preferably peracetic acid, orhydrogen peroxide for a suitable period, e. g., from about onehalf totwentyfour hours, the length of time depending upon the concentration ofoxygen-furnishing agent. When the oxidant is hydrogen peroxide, glacialacetic acid is a convenient reaction medium. When a peracid is employed,any of the customary organic solvents in which the starting steroid issoluble can carbon tetrachloride, ethylene dichloride, methylenechloride, mixtures of ether and chloroform, and others, with chloroformbeing preferred. It is sometimes desirable to add to the oxidizingmedium a small quantity of an alkali metal salt,

such as, for example, sodium acetate. Temperatures between about zeroand about 100 degrees centigrade can be conveniently used, with roomtemperature being entirely satisiactoryin most cases. In general, if ahigh temperature is employed, the reaction time may be somewhat reduced.The reaction mixture may be agitated continuously, as, for example, byshaking with a rotary shaking device or other conventional stirring oragitation means. temperatures above room temperature are employed, thereaction. may be conducted on a steam bath.

The 17 (20) -oxido-3,1la,20-triacyloxypregnanes can then be isolated inany convenient manner, such as by volatilizing the reaction medium,extracting the residue with chloroform, volatilizing the chloroform, andcrystallizing the residue from any organic solvent which is non-reactivewith the oxide. Alternatively, the reaction productcan be diluted withether, washed successively with dilute base and water, dried, evaporatedto dryness under vacuum, and dissolved in any convenient organic solventirom which the desired compound can be obtained upon crystallization. Itis sometimes preierred not to crystallize the product, as the residueobtained after removal of the solvent is of sufficient purityto be usedin subsequent reactions. Other recovery procedure includes pouring thereaction product into crushed ice or ice-water, filtering, and dryingthe precipitate.

The starting 3,11a,20-triacylXY-17(20) -pregnenes can be produced byvarious procedures.

3a,lls,20-triacyloxy 17(28) pregnenes. are conveniently prepared byheatinghalla-dihydroxypregnane-ZO-one or a 3a,llc-diacyloxypregnane-20-one, both prepared from progesterone as described below, with a largeexcess of an organic carboxylic acid anhydride in the presence. of anacid catalyst such as sulfuric acid, sulfonic acids and the like, withpara-toluenesulfonic. acid being preferred. The mixture is heated,usuallyat about 10c to 189 degrees centigrade, preferably at. theboiling point, until the anhydrlde is nearly completely removed bydistillation, which may require a period of aboutiour hours. The rateof. distillation may be faster or slower, and any period of about twohours to eight hours or even shorter or longer is operative. If theanhydride used has. a high boiling, point or is a solid, a, suitablesolvent such as toluene, xylene, aliphalic hydrocarbons or the like, maybe used as a temperature control. The preferred anhydride is aceticanhydride, but other anhydrides, such as propionic, butyric, Valerie,hexanoic, heptanoic, and octanoic anhydrides, as well as benzoic acidanhydride, ortho-toluic acid anhydridaand the like. are also. operative.The acid anhydrides can also be substituted with non-reactive groups,such be used, such as chloroform,

Alternatively, when as halo, alkyl, and methoxy, as in the case ofohloroacetic, ortho-toluic, or methoxybenzoic acid anhydrides. Under theconditions of the reaction, hydroxyl groups at carbon atoms three andeleven will be acylated. Starting 3a,11a,20- triacy1oxy17(29)-pregnenesmay also be prepared in the same manner fromlla-acyloxy-iiahydroxy-pregnane-20-ones, also prepared from progesteroneas described below.

The 3e,liii-dihydrOXypregnane-ZO-one, 311,111-diaoyloxypregnane-20-ones, and lla-acyloxy-fiahydroxypregnane 20 onesare prepared from progesterone by the following reactions. Progesteroneis oxidized to lla-hydroxyprogesterone by a fermentation process morefully described in Preparation 1. The lla-hydroxyprogesterone is reducedwith hydrogen in ethanol using a palladium-charcoal catalyst to givella-hydroxypregnane-3,20-dione. Reduction of theIla-hydroxypregnane-3,2G-dione with sodium borohydricle in dioXane givesthe desired 3a.,l1e-d'lhydroxypregnane-20-one. Acylation of thelie-hydroxypregnane 3,20 dione with an acylating agent, for example, anacid. anhydride, such as acetic anhydride, to give anllc-aeyloxypregnane- 3,20-dione, followed by reduction of the ll-acyloxypregnane-3,2G-dione with sodium borohydride in dioxane gives thedesired lla-acyloxy-fiahydroxypregnane-20-one. Subsequent acylation ofthe 1la.-acyloxy-3a-hydroxypregnane-20-one with an acylating agent, forexample, an acid anhydride, such as acetic anhydride, produces thedesired 3a,11a-diacyloxypregnane-20-one.

Starting 35,1la,20-triacyloxy-17(20) -pregnenes may be prepared fromlla-acyloxy-3d-hydroxypregnane-ZG-ones in the same manner as describedabove for the preparation of 3a,11a,20- triacyloxy-1'7(20)-pregnenesfrom lle-acyloxy- 3a-hydroxypregnene-2Gones. The lle-acyloxy-3B-hydroxypregnene-20ones are prepared by catalytic reduction oflla-acyloxypregnane-320- diones prepared from progesterone as describedabove, using hydrogen and a Raney nickel catalyst.

The following examples are illustrative of the process and products ofthe present invention, but are not to be construed as limiting.

Preparation 1.--1'1a-hydrozcyproyesterone To four liters of a- 32-48hour growth of culture REIT 6 (Rhizopus arrhizus strain) was added onegram of progesterone in fifty milliliters of acetone, providingasuspension of the steroid in the water of the culture. The culture wasthen incubated at room temperature for 48 hours. At the. end of thistime the pH of the medium was 3.5 and the fermentation liquor andmycelia were extracted successively with three one-liter portions, onetwo-liter portion, and one one-liter portion. oi methylene chloride. Themethylene chloride extracts were combined and washed with twoill-milliliter portions of two per cent. aqueous sodium bicarbonatesolution and three 500-milliliter portions of water. The metylenechloride extract was evaporated to dryness in vacuo and the solids takenup in fifty milliliters of methylene chloride. The solution wastransferred to a 100.- milliliter beaker and evaporated by a stream ofair. The solids, weighing 1.585 grams, were dissolved in fivemilliliters of hot methanol and allowed to cool slowly at roomtemperature, whereupon milligrams of crystalsseparated out. The motherliquor was. ireedoi solvent by aeration, dissolved in flitymillilitersofbenzene. and cluomatographed over alumina (M2031.

Fifty grams ofacid-washed alumina, dried at 45 degrees centigrade, wasused as adsorbent and IOU-milliliter portions of solvents were used todevelop the column. used were as follows: benzene, benzene, benzene plusper cent ether, benzene plus 5 per cent ether, benzene plus per centether, benzene plus 10 per cent ether, benzene plus 10- per cent ether,benzene plus 50 per cent ether,- benzene plus 50 per cent ether, ether,ether, ether plus 5 per cent chloroform, ether plus 5 per centchloroform, ether plus 10 per cent chloroform, ether plus 10 per centchloroform, ether plus 50 per cent chloroform, ether plus 50 per centchloroform, chloroform, chloroform, chloroform plus 5 per cent acetone,chloroform plus 5 per cent acetone, chloroform plus 10 per cent acetone,chloroform plus 10 per cent acetone, chloroform plus 50 per centacetone, chloroform plus 50 per cent acetone, acetone, acetone, acetoneplus 5 per cent methanol, acetone plus 5 per cent methanol, acetone plus10 per cent methanol, acetone plus 10 per cent methonal, acetone plus 50per cent methanol, acetone plus 50 per cent methanol. The chloroform andchloroform plus 5 per cent acetone eluates were combined, evaporated todryness, and the residue dissolved in two milliliters of hot methanoland filtered. After overnight refrigeration, 171 milligrams ofcrystalline 11ahydroxyprogesterone, melting at 166 to 167 de greescentigrade, was obtained. A recrystallized sample gave the followingconstants: melting point, 166-167 degrees centigrade; [M plus 175.9degrees (chloroform).

AnaZysis.Per cent calculated for CnHso O s: C,

76.4; H, 9.10. Found: C, 76.6; H, 8.92.,

The structure of..this.. product was further established by itsconversion, with chromic acid in acetic acid, to ll-keto-progesterone[Reichstein, Helv. Chim. Acta. 23, 684 (1940); ibid 26, 721 (1943)].

Preparation 2.-11a-hydrozcypregnane-3,20-dione A solution of 250milligrams of lla-hydroxyprogesterone from Preparation 1 in 100millilitersv of ethanol containing six drops of triethylamine wassubjected to hydrogenation at room temperature under a pressure of aboutten pounds of hydrogen in the presence of milligrams of a thirty percent palladium-charcoal catalyst'in a Parr apparatus with an auxiliarymercury manometer. The time required for the hydrogenation was abouttwenty minutes. The reaction mixture was filtered and the solvent wasevaporated toyield 265' milligrams of material melting at 145-185degrees centigrade. This product was extracted with a mixture of-tonemilliliter of' 'ether and nine milliliters of' Skelly Solve B.On'standing, the extract deposited eightymilli grams (32 per cent) 'oflla-hydroxy'pregnane 3,20-dioneas feathery needles which, melted at85-90 degrees centigrade. Recrystallization from a mixture of about sixdrops of ethyl acetate and five milliliters of Skelly Solve. B did notchange the melting point. I I f AnaZysis.-Per cent calculated forCell-1320a: C, 75.86; H, 9.70. Found: C, 76.13; H, 9.63.

Preparation 3.-3a-11a-dihydroa:ypregnane 20 one The solvents and theorder I hydride (assay 84 per cent) in five milliliters-of water. Themixture was stirred for one hour at fifty degrees centigrade, filtered,acidified with three normal aqueous hydrochloric acid solution andevaporated under reduced pressure. The residue was crystallized fromfifty milliliters of ethyl acetate to give 1.95 grams (36 per cent) of3a,1la-dihydroxypregnane-ZO-one, which melted at 180-182 degreescentigrade. An additional 0.2 gram melting at 181-183 degrees centigradewas obtained from the filtrate; total yield, 2.15 grams (40 per cent).

Preparation 4.11u-acetoxypregnane-3,20-dione:

Preparation 5.11a acetomy 3a hydromypregnane-ZO-one To a solution of 200milligrams (0.534 millimole) of 11a-acetoxypregnane-3,20-dione fromPreparation 4 dissolved in ten milliliters of peroxide-free dioxane atfifty degrees centigrade was added dropwise with stirring a solution of6.9 milligrams (0.152 millimole based on pure reagent) of sodiumborohydride (assay 83.5 per cent) in one milliliter of water. Themixture was stirred at fifty degrees centigrade for one hour andacidified by pouring into fifty milliliters of water containinghydrochloric acid. The oil which first separated crystallized onstanding; The solid was collected, washed with water, and dried underreduced pressure at fifty degrees centigrade. The yield of1la-acetoxy-3e-hydroXypregnane-20-one melting at 122-136 degreescentigrade was 156' milligrams." The crude product-was dissolved infifteen milliliters of benzene and chromatographed over 7.5 grams ofacidwashed alumina which had been dried at degrees centigrade. Thecolumn was developed-with two fifteen-milliliter portions of each of thefol.-, lowing seventeen solvents: benzene, benzene and 5, 10, and 50 percent ether, ether, ether and 5. l0, and 50- -per cent chloroform,chloroform, chloroform and5, 10, and 50 per cent acetone; acetoneand 5,10, and 50 per cent methanol, and methanol. The product appeared fromfraction 12 (ether and 5 per cent choloroform) through fraction 22(chloroform and 10 per cent acetone). Combination of these fractions andrecrystallization from ethyl acetate-Skelly Solve B gave 93 milligramsof product melting at -143 degrees centigrade. Two furtherrecrystallizations from isopropyl ether gave pure lla-acetoxy-3a-hydroxypregnane-20-one melting at 146-148 degrees centigrade.

Analysis-Per cent calculated for C23H3604Z C. 73.4; H, 9.64. Found: C,73.8; H, 9.61.

Preparation 6.-3a,1Ja-diccetQwypregnane-ZO-one I .Using the proceduredescribed in Preparation 4, the 11aeacetoxy-3a-hydroxypregnane-20-onealumnae 7 from Preparation 5 was esteriiied with acetic an hydridein'pyr-idine to yield 3c,ll-diacetoxypregname-'20 -cne.

Preparation 7.--3a.,11a,20-'triacetomy-17 ('20) pregnene temperature,poured into ice-water and the re suiting crystallin product collectedand washed with water. Recrystallization from acetonewater yielded 332milligrams of l3,l1a,20-triacetoxy-l'l-(JDl-pregnene, melting at 200-203degrees centigrade.

Preparation -8.-3e,1 1 ZO-triacetomy 47120) pregnene Preparation9.-3v.,11a,2D-triacetomy-17 (20) 'pregnene Using the same procedure asin Preparation '7,

242 grams =01 llwacetoxy-Bahydroxypregna.ne-

20-one from 'Prenara'tion 5 was treated with 1.06 grams ofpara-toluenesulfonic acid and 240 milliliters of acetic .anhydride. Theyield of 3u,l'1c,'20- triacetoxy-l'? (20) ing at 203-208 degreescentigrade.

Preparation 1 0.3u,1 '1 szfl-tripropionoxy-i 7 (2'0) pregnenc Using theprocedure descriloedin Preparation 7, 3a,lla-dihydroxypregnane 20-onefrom Preparation 3 is converted to Sa -11a, 20-tripropionoxy- 17(20")-pregnene with propionic anhydride in the presence ofpara-toluenesulfonic acid.

Preparation 11 .3a,1 1 adiacetomy-zO-propionory- 1 7 (20) -pregneneUsing the procedure described in Preparation 8,3a,ll-a-diacetoxypregnane-20-one from Preparatlon 6 is converted to3a,l1a-diacetoxy-20-proionoxy1'7(20) pregnene with propionic anhy-'dride the presence of para-toluenesulfonic acid.

Preparation 1 2 .3,1 1 a,20-triacetoxy-17 20 p'regnene Using theprocedure described in Preparation 9,SB-hydroxy-l1c-a-cet0xypregnane-20-one p r e pared by the reduction ofthe lla-acetoxypre'gnane-3,20-dicne of Preparation 4 with hydrogen attwo to three atmospheres pressure in methanol at room temperature usinga Raney nickel catalyst) is converted to '3B,1la,20triacetoxy-1'7(-20)pregnene with acetic anhydride in the presence of para-toluenesulfonicacid.

in the same manner as given above. other 3a to: 3B),11a;20-;tr-iacyloxy-l7 (:20) -pregnenes are3a,'1Ic-diacetQXypregnane-ZU-one A sample recrys- -pregnene was 1.54grarns,meltperature for two the solution was diluted with thirtymilliliters of prepared, including ilfilleflll-tripropionoxy-fl I 20)-pregnene, 3511a-diacetoxy-ZO-propionoxy- 17(20) 'pregn'ene'; 3.1,20dipropionoxy 11v.- acetoxy-17'(20) pregnene; 35,11d20-trioctanoyl-"oxy-ll ('20) -pregnene; 3a,2Q-di'octanoyloxy12lu-' propionoxy-1'l(20-=)-pregnene; 3a'benzoyloxy-11ee acetoxy-20-butyroyloxy-l7 (-20)-'pregnene; 311,110;- diacetoxy 20 benzoyloxy 17(20) pregnene; 3e,l1a;20tributyroy'lo'xy 17(20) pregnene; 3a,'lla;20-triyaleroyloXy-17(20l-pregnene; llama. 20 trihexanoyloxy 17(20') -':pregnene; 3 1.,11c.,- 20-triheptanoyloxy-l3t20) -'pregnene, and Belle,-20-trioctanoylo'xy-17(20) -pregnene.

Example 1 .--17 (20.) -O$id03u,11a,ZD-tTiIZCEtOQJypregnane One andone-'haligrams of 3a,1le,20-triac'etoxy- 17(20) -pregnene (fromPreparation '7, .8, or 9) was dissolved'in 7.5 milliliters ofchloroform, and the solution was cooled in an ice bath to about fivedegrees 'centigrade. Three and three-tenths milliliters of commercialgrade forty per cent 'peracetic acid solution'in which 100 milligram ofsodium acetate hadibe'en dissolved was added, and the resulting mixturewas then shaken on a mechanical shaking machine for about two hours atroom temperature to complete the reaction. The mixture containing thecrude product was diluted with fifty milliliters of methylene chloridand then washed with several 25-milliliter portions of ice-cold five percent aqueous sodium hydroxide solution followed loy 25-milliliterportions of water until the wash solution was neutral to pH test paper.The neutral sclution'was dried with anhydrous sodium sulfate and thenfiltered to remove the drying agent. The white crystalline residuobtained on evaporating the "solvent from the clear, dry solution meltedat 210-213 degrees centigrade. Recrystallization from :a mixture of"ethyl acetate and Skelly Solve "B gave fluffy needle of 17(20)-oxido-3a,1la,20-triacetoxypregnane melting at 214-217 degreescentigrade.

Analysis-Per cent calculated for Carl-14007: C. 68.04; H, 3.46. Found:C, 68.33; H, 8.62.; C, 67.90.;

Example -Z.--17-(20)-0.'12idO-3a,1ImZU-tTilZCBiO-TIZI- pregnane One gramof 3a,l'1a,20-triacetoxy-17(20.) -pregnene from Preparation 7, 8, or 9.)was dissolved in fifteen milliliters of benzene and five milliliters ofa two-molar solution of perbenzoic acid .in hem zene was added. Afterstanding at room temhours to complete the reaction,

benzene. The crude 17(20)-0XidO-3u,1lu,20tri acetoxypregnane, melting at211-214 degrees centigrade, was obtained using the same procedure forisolation as in Example 1.

Example 3.-1 7 (20) maniac-3a,! 1 ago-mpropionomypr gnane Example4.-3a.,11adi008t0$1I-17 (20) -oa:id o- '20-propionoxypregnan'e Using theprocedure described in Example 2, Balls cli'acetoxy 20 nropionoxy1"'l'(20l pregnene from Preparation 11 is converted to 3a.,11a.diacetoxy 17(20) oxido 20 propionoxypregnane by oxidation withperbenzoic acid.

Example 5 .1 Z -oa:z'do-3fi,11 a,20-triacetozrypregnane Using theprocedure described in Example 1, 3 3,11a,24)-triacetoxy-17(20)-pregnene from Preparation 12 is converted to 17 (20) -o.xido-3B,11a,20-triacetoxypregnane by oxidation with peracetic acid in the presence ofsodium acetate.

Example 6.1 7 (20) mama-313,11 a,20-tmacetoxypregnane pregnane;17(20)-oxido-3a,11c,20-tributyryloxy- U pregnane; 17(20)-oxido-3a,11a,20-trivaleryloxypregnane;17(20)-oxido-3a,11a,20-trihexanoyloxypregnane; 17(20)-0xido-3a,11a,20-triheptanoyloxypregnane 17 (2'0) -OXidO-3a,11a,20-t1i00t8.11- oyloxypregnane, and the like.

It is to be understood that the invention is not to be limited to theexact details of operation or exact compounds shown and described, asobvious modifications and equivalents will be apparent to We claim:

1. A 17(20)-oxido-3,11a,20-triacyloxypregnane, wherein the acyloxygroups have the formula AcO, Ac being the acyl radical of a hydrocarboncarboxylic acid containing from one to eight carbon atoms, inclusive.

2. A 17(20)-oxido-3,11a,20-triacyloxypregnane, wherein the acyloxygroups have the formula AcO, Ac being the acyl radical of a hydrocarboncarboxylic acid containing from one to eight carbon atoms, inclusive,and wherein the acyloxy groups at carbon atoms three, eleven, and twentyare derived from the same organic carboxylic acid.

3. A 17(20)-oxido-3,1111,20-triacyloxypregnane, wherein the acyloxygroups have the formula AcO, Ac being the acyl radical of a hydrocarboncarboxylic acid containing from one to eight carbon atoms, inclusive,and wherein the acyloxy groups at carbon atoms three, eleven, and twentyare derived from two different organic carboxylic acids.

4. A 17(20)-oxido-3,11a,20-triacyloxypregnane wherein the acyloxy groupshave the formula AcO, Ac being the acyl radical of a hydrocarboncarboxylic acid containing from one to eight carbon atoms, inclusive,and wherein the acyloxy groups at carbon atoms three, eleven, and twentyare derived from three different organic carboxylic acids.

5. A 17(20) oxido 3a,11a,20 triacyloxypregnane wherein the acyloxygroups have the formula AcO, Ac being the acyl radical of a hydrocarboncarboxylic acid containing from one to eight carbon atoms, inclusive,and wherein the acyloxy groups at carbon atoms three, eleven, and twentyare derived from the same organic carboxylic acid.

6. A 17(20) oxido 3fl,11a,20 triacyloxypregnane wherein the acyloxygroups have the formula AcO, Ac being the acyl radical of a hydrocarboncarboxylic acid containing from one to eight carbon atoms, inclusive,and wherein the acyloxy groups at carbon atoms three, eleven, and twentyare derived from the same organic carboxylic acid.

7. 17(20) -oxido-3c,11c,20-triacetoxypregnane.

8. 17(20) oxido 3a,11a,20 tripropionoxypregnane.

9. 3a,11a diacetoxy 17(20) oxido 20 propionoxypregnane.

10. 17(20) oxido 3B,11a,20 triacetoxy 17(20) -pregnane.

FRANK H. LINCOLN, JR. GEORGE B. SPERO.

References Cited in the file of this patent UNITED STATES PATENTS

1. A 17 (20)-OXIDO-3, 11A,20-TRIACYLOXYPREGNANE, WHEREIN THE ACYLOXYGROUPS HAVE THE FORMULA ACO, AC BEING THE ACYL RADICAL OF A HYDROCARBONCARBOXYLIC ACID CONTAINING FROM ONE TO EIGHT CARBON ATOMS, INCLUSIVE.